Carbenes additions to double bonds

Photolytically generated carbene, as mentioned above, undergoes a variety of undiscriminated addition and insertion reactions and is therefore of limited synthetic utility. The discovery (3) of the generation of carbenes by the zinc-copper couple, however, makes carbene addition to double bonds synthetically useful. The iodo-methylzinc iodide complex is believed to function by electrophilic addition to the double bond in a three-center transition state giving essentially cis addition. Use of the... 

These cycloadditions lead to the formation of three membered rings commonly seen in the carbene addition to double bonds. 

The model predicts k2l). This is found to be consistent with the fact that carbene insertion into a C-H bond is slower than carbene addition to double bonds. The agreement with experimental data was satisfactory. The carbene insertion reaction in olefins, as described by Chang,predicts a redistribution of olefinic species, but no net increase in the production of olefins. This was corrected for by Anthony. 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

For reviews of the stereochemistry of carbene and carbenoid addition to double bonds, see Moss Set. Org. Transform. 1970, /, 35-88 Closs Top Stereochem. I960 3, 193 235. For a discussion of enantioselectivity in this reaction, see Nakamura Pure App. Ckem. 1978,50, 37. 

The most common synthetic reaction of carbenes is their addition to double bonds to form cyclopropane rings. For example, dibromocarbene adds to cyclohexene to give an interesting bicyclic compound. 

It is known that most carbenes, including arylcarbenes, undergo intermolecular electrophihc addition to double bonds 87). Then we might expect that if arylcarbenes cyclize intramolecularly to bicycloheptatrienes [e.g. Eqs. (12), (13)], this should be an electrophilic addition, and the carbene should add preferentially to the double bond of highest bond order 68>. Gas-phase experiments with substituted naphthylcarbenes indicated that such was the case 88). 

Although the addition of carbene to a double bond to make a cyclopropane is well known, it is not particularly useful synthetically because of the tendency for extensive side reactions and lack of selectivity for thermally or photochemically generated carbenes. Similar processes involving carbenoids (species that are not free carbenes) are much more useful from the preparative standpoint [91,92]. For example, metal catalyzed decomposition of diazoalkanes usually results in addition to double bonds without the interference of side reactions such as C-H insertions. Consider the possible retrosynthetic approaches to a 1,2-disubstituted cyclopropane shown in Figure 6.8. Disconnection a entails the addition of a methylene across a double bond, a conversion that is often stereospecific e.g., the Simmons-Smith reaction [93]). Disconnections b and c are more problematic, since the issue of cis/trans product isomers (simple diastereoselection) arises. 

Insertion and addition are definitely two of the most fundamental reaction modes for both carbenes and silylenes. While the most convenient method for trapping carbenes involves their addition to double bonds to give stable cyclopropane derivatives, the corresponding method for trapping silylenes is generally complicated by the fact that most of the silacyclopropanes are unstable species and therefore undergo various secondary processes. In practice, with the exception of alkynes and coqjugated dienes, addition reactions are rarely employed to intercept silylenes. 

The effect of multiplicity of carbenes on their reactivity is most vividly marked in the following features rationalized by Skell et al. from experimental data [37-39]. First, the reaction of carbenes occurs in the singlet electron state at a much faster rate than in the triplet, with the absolute rates of typical reactions of addition to multiple bonds and of insertion into the C—H bonds exceeding, under normal conditions, the rate of intercombination conversion. Secondly, the singlet carbenes are characterized by one-step stereospecific addition to double bonds, as, for instance, in the cyclopropanation reaction, while the triplet carbenes react in a nonstereospecific way to form first an intermediate biradical through addition to one of the atoms of the double bond. The formation of a trimethylene radical, in the course of reaction of triplet methylene ( B ) with ethylene, has been confirmed by semiempirical [40, 41] and ab initio [42, 43] quantum chemical calculations. 

Aziridines can be formed by nitrene (-like) additions to double bonds, or by carbene (-like) additions to imines. Both processes especially the latter one can also occur by a stepwise addition-elimination process [172]. Similar to cyclopropa-nations, aziridinations of imines can foUow two protocols alkylation-deprotonation-substitution and sulfide reactions with metallocarbenes. 

Comments The diene A is symmetrical so it doesn t matter which double bond is attacked by the carbene. On the other hand, it may be difficult to stop carbene addition to the second double bond. The only control over the stereochemistry will be that the trans compound we want is more stable. Japanese chemists have recently synthesised optically active trans chrysanthemic acid by this route (Tetrahedron Letters. 1977, 2599). 

Chlorins are also accessible by carbene additions to C-C double bonds on the periphery of metalloporphyrins. The most effective reaction on a preparative scale is the addition of ethyl diazoacetate in refluxing benzene to copper octaethylporphyrin (4) or meso-tetraphenylpor-phyrin in the presence of copper(I) iodide,100108b 110 which gives a diastereomcric mixture of chlorins, e.g. 5. 

Woodworth, based on the common reaction of addition of carbenes to double bonds to form cyclopropane derivatives (15-50). If the singlet species adds to cis-2-butene, the resulting cyclopropane should be the cis isomer since the movements of the two pairs of... 

A short paper, the beginning of whose title is designed to catch the eye, A universal rotane synthesis announced the synthesis of [6]rotane 85 for the first time via carbene addition to 84, 1). An alternative method was to add carbene to a starting material 86, containing two double bonds 32. ... 

Several reviews on the synthesis of aziridines have been published in the previous year. These publications include a review on the silver catalyzed addition of nitrenes (among other intermediates such as carbene) across a double bond <06EJOC4313> a review on sulfur ylide addition to imines to form aziridines <06SL181> a review on nitrogen addition across double bonds <06ACR194> a general review on functionalization of a,p-unsaturated esters with some discussion of aziridination <06TA1465>... 

The two nonbonded electrons of a carbene can be either paired or unpaired. If they are paired, the species is spectrally a singlet, while, as we have seen (p. 193), two unpaired electrons appear as a triplet. An ingenious method of distinguishing between the two possibilities was developed by Skell,202 based on the common reaction of addition of carbenes to double bonds to form cyclopropane derivatives (5-50), If the singlet species adds to cis-2-butene, the resulting cyclopropane should be the cis isomer since the movements of... 

In a logical continuation of this work, carbene addition to an iron-iron double bond has also been exploited for the simple synthesis of the first /. -methylene complex in the nitrosyl series. The readily available /x-nitrosyliron complex [(Tj5-C5H5)Fe(/u.-NO)]2 (26) exhibits the same structural features as the rhodium dimer 21 (157) and reacts with diazomethane in the temperature range -80-25°C to give the expected /z-methylene derivative 27 (Scheme 14) as a black, air-stable compound in... 

Comments The diene A is symmetrical so it doesn t matter which double bond is attacked by the carbene. On the other hand, it may be difficult to stop carbene addition to the... 

An anomalous cycloaddition is the insertion of a carbene into an alkene. Some cheletropic reactions are straightforwardly allowed pericyclic reactions, which we can illustrate with the drawing 6.127 for the suprafacial addition of sulfur dioxide to a diene, and with the drawing 6.128 for the 8-electron antarafacial addition of sulfur dioxide to a triene. The problem comes with the insertion of a carbene into a double bond, which is well known to be stereospecifically suprafacial on the alkene with singlet electrophilic carbenes [see (Section 4.6.2) page 149]. This is clearly a forbidden pericyclic reaction if it takes place in the sense 6.129. 

The addition of dihalocarbenes to double bonds occurs stereospecifically to give cyclopropane derivatives [68J. The reaction appears to have electrophilic character even though the electronic state of the carbene is uncertain (cf. p. 341). Again the direction of attack on the double bond is subject to steric control. The diene (2) for example, reacts with di-bromocarbene to give first the 2ct,3[Pg.294]

This is an example of the most important reaction of methylene and other carbenes addition to the carbon-carbon double bond. Its most striking feature is that it can occur with two different kinds of stereochemistry. 

Oxepin 404 was prepared by the reaction of ethyl diazopyruvate with 1,3-butadiene in 26% yield. The reaction involves a carbene addition to the double bond with formation of a mixture of cis- and trans-2-oxo-2-(2-... 

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